The Great Influenza (66 page)

Flexner urged him (indeed, all but ordered him) to take the Iowa position. It was an extraordinary offer: $10,000 a year salary (more than double the median income for physicians) and a free hand in organizing a department. Flexner assured him that he still believed he had great gifts. Great gifts. He could still make a huge contribution, a significant and important contribution. At Iowa he could become a major figure, inspire respect, and be far happier.

Lewis listened quietly and said little. He did not remonstrate or argue. He was almost passive, yet firm. There was a cold, unreachable center within him. Regarding Iowa, that was settled. He would reject the offer. He had no interest in anything but the laboratory. He hoped in the next year to justify reappointment.

After the conversation Flexner was frustrated, frustrated and angry. 'I put all the pressure I could upon him but without avail,' he wrote Smith. 'My notion is our obligations to Lewis are now fulfilled and that unless a great change takes place it will be our duty to act decisively next spring. He has been a real disappointment to me' . I left no doubt as to the risk he takes, and he left me no doubt that he understands and accepts that risk.'

* 

A few months before Flexner's brutal conversation with Lewis, Hideyo Noguchi had gone to Ghana to investigate yellow fever. Noguchi was as close to a pet as Flexner had. They had first met almost thirty years earlier, when Flexner was still at Penn and gave a speech in Tokyo. Uninvited, Noguchi had followed him to Philadelphia, knocked on his door, and announced he had come to work with him. Flexner found a position for him, then took him to the Rockefeller Institute. There Noguchi had developed an international reputation, but a controversial one.

He had done real science with Flexner, for example, identifying (and naming) neurotoxin in cobra venom. And he had claimed even more significant breakthroughs on his own, including the ability to grow polio and rabies viruses. (He could not have grown them with his techniques.) Rivers, also at Rockefeller and the first person to demonstrate that viruses were parasites on living cells, questioned those claims. Noguchi responded by telling him that a man who had done research for a long time had scars that he could never get rid of. Later Rivers discovered a significant unrelated mistake in his own work and confessed to Noguchi that he planned to retract his paper. Noguchi advised against it, saying it would take fifteen years for anyone else to find out he was wrong. Rivers was astounded, later saying, 'I don't think Noguchi was honest.'

Noguchi's most important claim, however, was to have isolated the pathogen that caused yellow fever. It was a spirochete, he said, a spiral-shaped bacterium. Years before, Walter Reed had seemed to prove that a filterable virus caused the disease. Reed was long dead, but others attacked Noguchi's findings. In response to one such attack, Noguchi wrote Flexner, '[H]is objections were very unreasonable' . I am not certain whether these Havana men are really interested in scientific discussion or not.'

Noguchi did not lack courage. And so he went to Ghana to prove himself correct.

In May 1928 he died there, of yellow fever.

Noguchi's death came one month before Flexner and Lewis had their conversation. It attracted international attention, made the front pages of newspapers around the world, inspired glowing tributes in all the New York papers. For Noguchi, it was a Viking funeral, a blazing glory that obliterated all questions about the quality of his science.

The entire Rockefeller Institute reeled from the loss. Despite any scientific controversies, Noguchi had been buoyant, enthusiastic, always helpful, universally liked. Both Flexner and Lewis suffered in particular. Noguchi had been, literally, like a son to Flexner. Lewis had known him well, very well, going back to his first happy days in New York.

Noguchi's death also left open the question of whether he had in fact isolated the pathogen that caused yellow fever. The institute wanted that question answered.

Shope volunteered to do it. He was young and believed himself invulnerable. He wanted action. He wanted to investigate yellow fever.

Flexner refused to allow him to go. Shope was also only twenty-eight years old, with a wife and an infant son. It was too dangerous.

Then Lewis volunteered. The scientific question remained, and it was a major one. Who was more qualified to investigate it than he? He had proven himself expert at cultivating bacteria and, even more important, he had proven that polio was a viral disease. Noguchi notwithstanding, it seemed a virus did cause yellow fever. And, important as the question was, it also had built-in limits; it was the kind of narrow and focused science that Flexner still had faith in Lewis to answer.

Lewis's wife, Louise, objected. The laboratory had taken him away from her and their two children enough. She was already furious at him for once again declining the Iowa position. But
this
' this was something else.

Lewis had never listened to her. They had not had a real marriage for a long time. For him, this solved every problem. If he succeeded, he would restore himself in Flexner's eyes. Five years before he had resigned from the Phipps Institute and simultaneously withdrawn his acceptance of the Iowa offer without any other prospects. All that he had done in order to do the one thing he loved, return to the laboratory. He was willing to gamble again. He was energized again. And he was more desperate than ever.

Instead of Ghana, however, he would go to Brazil. A particularly virulent strain of yellow fever had surfaced there.

* 

In late November 1928, Flexner came to Princeton to see Lewis off. Flexner's attitude toward him had already seemed to change. He was willing again to talk about the future. He also wanted, he said, to 'learn about Shope's Iowa work.' Shope had recently observed an extraordinarily violent influenza epizootic (an epidemic in animals) in swine. The overall mortality of the entire local pig population had reached 4 percent; in some herds mortality had exceeded 10 percent. That very much sounded like the influenza pandemic in humans a decade earlier.

A month later Lewis sailed for Brazil. On January 12, 1929, Frederick Russell, the colonel who had organized much of the army's scientific work for Gorgas and who now worked for a Rockefeller-sponsored international health organization, received a cable saying Lewis had arrived and was well. The institute relayed the news to his wife, who had been so angry at Lewis's departure that she had wanted nothing to do with the Rockefeller Institute and returned to Milwaukee, where both she and Lewis had grown up. Each week Russell was to receive news of Lewis and send it on to her.

Lewis located his laboratory in Belem, a port city on the Para River, seventy-two miles from the ocean but the main port of entry into the Amazon Basin. Europeans settled there in 1615, and a rubber boom in the nineteenth century had filled the city with Europeans while Indians went back and forth into the interior in dugout canoes. It was steamy, equatorial, and received as much precipitation as any area in the world.

On February 1, Lewis wrote Flexner, 'Arrived here on Tuesday and went right to work' . [H]ave been setting up my own shop here, awaiting materials, having additional screening prepared, etc' . Should be started at something by early next week I hope.'

He seemed the old Lewis, energetic and confident. And each week Russell received a two-word wire: 'Lewis well.' He received them through February, March, April, and May. But if Lewis was well, he sent no word about his research; he gave no sign that work was going well.

Then, on June 29, Russell sent a note hand-delivered by messenger to Flexner: 'The following message from Rio de Janeiro, regarding Dr. Paul Lewis, was sent to me today, with the request that it be delivered to you. 'Lewis's illness began on June 25th. Doctors state it to be yellow fever. Condition of June 28th, temperature 103.8, pulse 80' .' The Foundation is sending the message to Dr. Theobald Smith and also to Mrs. Lewis at Milwaukee.'

Even as Russell sent that note to Flexner, Lewis was in agony. He had vomited violently, the nearly black vomit of the severe cases; the virus attacked the mucosa in his stomach, which bled, giving the vomit the dark color; it attacked the bone marrow, causing violent aching. An intense, searing headache gave him no rest, except perhaps when he was delirious. He had seizures. His colleagues packed him in ice and tried to keep him hydrated but there was little else they could do.

The next day another wire came: 'Lewis condition critical. Anuria supervened Saturday.'

His kidneys were failing and he was producing no urine. All the toxins that the body normally rid itself of were now building up in his system. Later that same day, Russell received a second wire: 'Lewis on fourth day of illness. Marked renal involvement.' He was becoming jaundiced, taking on the classic color that gave the disease its name. Symptom by symptom, step by step his body was failing.

June 30, 1929, was a Sunday. All day Lewis suffered, writhed in delirium. He went into a coma. It was his only relief. It was the fifth day of his illness. There would not be a sixth.

Shortly before midnight Dr. Paul A. Lewis found release.

An unsigned wire to Russell reported, 'Typical yellow fever. Probably laboratory infection. Wire instructions regarding body.'

Shope walked down Maple Street on the edge of the Princeton campus to inform Lewis's wife, who had come back from Milwaukee, and son Hobart, now a college student who had remained in Princeton.

Lewis's widow gave simple and explicit instructions. She was returning immediately to Milwaukee and wanted the body shipped directly there, where those who cared about Paul were. She specifically stated that she wanted no memorial service held at the Rockefeller Institute, in either New York or Princeton.

There was none.

* 

Shope accompanied the body to Wisconsin. The business manager of the Rockefeller Institute asked him, 'I wonder if you could arrange when you arrive to order some flowers for the service for Dr. Lewis.'

The flowers came, with a card signed 'the Board of Scientific Directors of the Rockefeller Institute.'

Lewis's daughter, Janet, wrote the thank you note, addressing it 'Dear Sirs.' Her mother could not bring herself to have any contact with the institute, particularly a thank you note. The institute paid Lewis's salary to her through June 1930 and also paid his son Hobart's college tuition. (Like his grandfather and aunt Marian, the first woman to graduate from Rush Medical College in Chicago, he became a physician) but a clinician, not a scientist.)

In the next report to the Board of Scientific Directors of the Rockefeller Institute (a board which now included Eugene Opie, whom Lewis had recruited as his successor at Phipps) Flexner noted that one scientist's resignation 'which is much regretted, left the study of light phenomena unprovided for.'

Lewis had originally suggested that work to Flexner. Flexner mentioned a 'recrudescence of poliomyelitis.' Lewis had proved that a filterable virus caused that disease.

Flexner went through item after item concerning the institute. He pointed out 'a pressing problem was the one in connection with the still unfinished work of Dr. Noguchi.' He made no mention of Paul A. Lewis, no mention of Dr. Lewis at all.

Later Flexner received Lewis's autopsy report and news that researchers at the institute in New York had succeeded in transmitting Lewis's virus (they called it 'P.A.L.') to monkeys and were continuing experiments with it. Flexner wrote in reply, 'Thank you for sending me the report on the comparison of the Rivas and P.A.L. strains of yellow fever virus. At your convenience I should like to talk over the report with you. Dr. Cole thinks white paint and some other improvements desirable in your animal quarters. Has he spoken with you about them?'

* 

Lewis had worked with deadly pathogens his entire adult life and had never infected himself. Since Noguchi's death everyone working with yellow fever took special care.

In the five months Lewis worked in Brazil he did not report any details of his research and his laboratory notes provided almost no information about it. He died from a laboratory accident. Somehow he gave yellow fever to himself.

Shope later told his sons a rumor that Lewis, who smoked often, had somehow contaminated a cigarette with the virus and smoked it. The virus entered the bloodstream through a cut on his lip. David Lewis Anderson recalls that his father, Lewis's friend in Philadelphia, also blamed cigarettes for Lewis's death.

Three years earlier Sinclair Lewis, no relation, won the Pultizer Prize for his bestselling novel
Arrowsmith,
a novel about a young scientist at a fictionalized version of the Rockefeller Institute. Everyone in medical science, especially at the institute, knew that novel. In it the main character's wife dies from smoking a cigarette contaminated by a deadly pathogen.

Flexner wrote an obituary of Lewis for
Science
in which he referred to 'the important observations made by him in association with Sewall Wright on the hereditary factors in research in tuberculosis.' Lewis's work with Wright had been carried out in Philadelphia; Flexner made no mention of anything Lewis had done in the five years since his return to the institute.

Meanwhile, Shope returned to Iowa to explore further this swine influenza, to observe still another epidemic among pigs.

* 

In 1931, two years after Lewis's death, Shope published three papers in a single issue of the
Journal of Experimental Medicine
. His work appeared in good company. In that same issue were articles by Avery, one of the series on the pneumococcus that would lead to his discovery of the transforming principle; by Thomas Rivers, the brilliant virologist; and by Karl Landsteiner, who had just won the Nobel Prize. All of these scientists were at the Rockefeller Institute.

Each of Shope's articles was about influenza. He listed Lewis as the lead author on one. He had found the cause of influenza, at least in swine. It was a virus. We now know that the virus he found in swine descended directly from the 1918 virus, the virus that made all the world a killing zone. It is still unclear whether humans gave the virus to swine, or swine gave it to humans, although the former seems more likely.